This invention relates to the preparation of powders, particularly for the administration of pharmaceuticals to humans.
Pharmaceuticals are often unstable compounds that degrade rapidly during processes that lead to a powder form of the pharmaceutical. Since the pharmaceutical compound is usually carried in an aqueous solution, and the aqueous solution must be dried to form the powder, the required desiccation or drying process may easily damage the pharmaceutical. At the same time, if the process of forming the powder takes too long, or is too energy consuming, the process may become uneconomic.
Freeze drying (lyophilization), which has conventionally been used to prepare pharmaceutical powders, provides a two step preservation and dehydration process in which the product is first frozen and the water is then removed as vapor from the frozen state. As the water passes from the solid phase directly into the vapor phase, it is necessary that the vapor pressure and the temperature of the sublimation zone is held below those of the triple point on the phase diagram for water. The temperature (<<0° C.) and the maintenance of the frozen state lead to very low driving forces for heat and mass transfer and therefore, often to very low drying rates and very long drying times. Thus, despite its capability of providing a very high-quality dehydrated product, freeze-drying has been and remains highly energy-intensive and consequently, is a very expensive dehydration process.
Freeze drying conventionally is carried out in a vacuum, but may also be carried out at or near atmospheric pressure. Atmospheric freeze-drying has been shown to have the added advantage of increasing transfer coefficients and improving the uniformity of the product during lyophilization. For example, Meryman, H. T., Sublimation freeze-drying without vacuum. Science, 130 (1959) 628-629 proposed an atmospheric freeze-drying process in which the partial pressure of water in the drying chamber is held at very low value and he suggested that such a process should be based on the principle of convective freeze drying, i.e. a cold air steam, kept dry by a molecular sieve desiccant or by a refrigerated condenser, should be circulated. More recently, Leuenberger, H., Spray freeze-drying—the process of choice for low water soluble drugs, Journal of Nanoparticle Research, 4:111-119, 2002 has also identified that spray freeze drying helps preserve pharmacological activity of drugs by stabilization in an appropriate matrix.
Despite the potential advantages of atmospheric lyophilization, the challenge still remains to provide a combination of spray-freezing solution/suspension into liquid and atmospheric freeze-drying that meets industrial demands for a pharmaceutical powder process that maintains drug bioactivity at low economic cost.